Diabetes is divided into two types—i.e., insulin-dependent type 1 diabetes and insulin-independent (insulin-resistant) type 2 diabetes which is found in 90% or more of diabetic patients.
GPR120 agonists, which are noted for possible treatment of type 2 diabetes, are known to have (1) an antidiabetic effect caused by the actions of increasing incretin hormone in intestinal cells, (2) anti-inflammatory action in macrophages, and (3) an action of improvement on insulin resistance in lipocytes. They are also known as a possible treatment of type 1 diabetes due to the improvement on proliferation of pancreas cells by anti-inflammatory action.
G protein-coupled receptor 120 (GPR120) is expressed copiously in the intestines, lungs, adipose tissue, and macrophages which induce inflammation, and is activated by long-chain free fatty acid (FFA). GPR120 stimulates the secretion of glucagon-like peptide-1 (GLP-1) by FFA. GLP-1, an incretin hormone, is known to stimulate the secretion of insulin in the pancreas dependently on blood glucose level, and also to have the effect of improvement of insulin resistance, proliferation of β-cells, appetite loss and increase of satiety. Recently, GPR120 is known to relate with improvement of insulin resistance and anti-inflammatory effect, and therefore, it is regarded as a target for developing a drug to effectively improve insulin resistance, type 2 diabetes and obesity involving low-level chronic inflammation. Furthermore, in animal experiments of type 1 diabetes, GPR120 agonists are reported to improve the secretion of insulin by the action of proliferation of β-cells.
Since GPR 120 agonists also have anti-inflammatory action, they are reported to be a possible treatment of inflammation-related diseases for example, steatohepatitis, rheumatoid arthritis, etc.
Considering the above, researches on GPR120 agonists are actively in progress. In the representative compounds presented as GPR120 agonists, two aryl groups are connected with a center bridge structure, and the characteristic feature is that one of two aryl groups is substituted by carboxylic acid. GPR120 agonist compounds are disclosed in WO2011/159297, WO2010/080537, WO2010/104195, WO2010/048207, WO2009/147990, WO2008/066131, WO2008/103500 and WO2008/139879.